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Activity-dependent dynamics and sequestration of proteasomes in dendritic spines

Bingol, Baris and Schuman, Erin M. (2006) Activity-dependent dynamics and sequestration of proteasomes in dendritic spines. Nature, 441 (7097). pp. 1144-1148. ISSN 0028-0836. https://resolver.caltech.edu/CaltechAUTHORS:20150319-093324186

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Abstract

The regulated degradation of proteins by the ubiquitin proteasome pathway is emerging as an important modulator of synaptic function and plasticity. The proteasome is a large, multi-subunit cellular machine that recognizes, unfolds and degrades target polyubiquitinated proteins. Here we report NMDA (N-methyl-D-aspartate) receptor-dependent redistribution of proteasomes from dendritic shafts to synaptic spines upon synaptic stimulation, providing a mechanism for local protein degradation. Using a proteasome-activity reporter and local perfusion, we show that synaptic stimulation regulates proteasome activity locally in the dendrites. We used restricted photobleaching of individual spines and dendritic shafts to reveal the dynamics that underlie proteasome sequestration, and show that activity modestly enhances the entry rate of proteasomes into spines while dramatically reducing their exit rate. Proteasome sequestration is persistent, reflecting an association with the actin-based cytoskeleton. Together, our data indicate that synaptic activity can promote the recruitment and sequestration of proteasomes to locally remodel the protein composition of synapses.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nature04769 DOIArticle
http://www.nature.com/nature/journal/v441/n7097/full/nature04769.htmlPublisherArticle
http://www.nature.com/nature/journal/v441/n7097/suppinfo/nature04769.htmlPublisherSupplementary Information
http://rdcu.be/cmmLPublisherFree ReadCube access
ORCID:
AuthorORCID
Schuman, Erin M.0000-0002-7053-1005
Additional Information:© 2006 Nature Publishing Group. Received 28 December 2005; Accepted 30 March 2006. We thank the Kloetzel, Masucci and Kennedy laboratories for providing the Rpt1(CIM5)–GFP, Ub^(G76V)–GFP and mRFP clones, respectively. We also thank members of the Schuman laboratory, especially C.-Y. Tai and S. Kim, and former member G. Patrick for discussions. E.M.S. is an Investigator of the Howard Hughes Medical Institute.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:7097
Record Number:CaltechAUTHORS:20150319-093324186
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150319-093324186
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55924
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Mar 2015 18:30
Last Modified:09 Mar 2020 13:19

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